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Validated All-in-One™ qPCR Primer for MDM2(NM_002392.5) Search again
Product ID:
HQP102206
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ACTFS, HDMX, LSKB, hdm2
Gene Description:
MDM2 proto-oncogene
Target Gene Accession:
NM_002392.5(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
This gene is a target gene of the transcription factor tumor protein p53. The encoded protein is a nuclear phosphoprotein that binds and inhibits transactivation by tumor protein p53, as part of an autoregulatory negative feedback loop. Overexpression of this gene can result in excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. This protein has E3 ubiquitin ligase activity, which targets tumor protein p53 for proteasomal degradation. This protein also affects the cell cycle, apoptosis, and tumorigenesis through interactions with other proteins, including retinoblastoma 1 and ribosomal protein L5. More than 40 different alternatively spliced transcript variants have been isolated from both tumor and normal tissues. [provided by RefSeq].
Gene References into function
- mdm2 has binding sites for phosphorylation by CK2
- protein interaction mapping with mouse p19ARF
- a regulatory loop exists in which Hdm2 regulates the intracellular localization of Hdmx, and nuclear Hdmx regulates several functions of Hdm2 (ubiquitin ligase activity and p53 nuclear export).
- higher expression in childhood leukemias with poor prognosis compared to long-term survivors
- Normal cells may induce full-length MDM2 in response to oncogenic challenges to protect against premature cell cycle progression. MDM2 is regulated by p53 especially durnig embryogenesis where MDM2 function is inhibited.
- findings suggest that amplification and overexpression of HMGIC and possibly MDM2 might be important genetic events that may contribute to malignant transformation of benign pleomorphic adenoma
- absence of nucleolar or nucleoplasmic p14ARF/Hdm2 complexes in Reed Sternberg cells in Hodgkin's lymphoma associated with expression of alternatively spliced Hdm2 transcripts
- MDM2 overexpression correlates with favorable prognosis in human breast cancer
- p53 ativation by nitric oxide involves down-regulation
- role for IGF-I in the regulation of the MDM2/p53/p21 signaling pathway during DNA damage
- Antisense of MDM2 enhance therapeutic efficiency of irinotecan in colon cancer
- Akt enhances Mdm2-mediated ubiquitination and degradation of p53.
- description of a novel MDM2 binding interface in p53 that plays a regulatory role in MDM2-dependent ubiquitination of p53
- Novel splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines
- MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding
- Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators.
- promoter usage of mdm2 gene in human breast cancer
- Phosphorylation of HDM2 by Akt, and protein binding
- summarize the current understanding of post-translational modifications and their effect on conformation-based functional relationship between Mdm2 and p53
- MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding sites; a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia.
- Cyclin G expression also results in reduced phosphorylation of human Hdm2 at S166.
- p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products.
- expression significantly correlated with favorable prognosis in esophageal squamous cell carcinoma in p53-negative patients but not p53-positive patients
- MDM2 can inhibit PCAF-mediated p53 acetylation and activation.
- MDM2 inhibition of p53 induces E2F1 transactivation via p21
- RNA polymerase III transcription can be derepressed by hdm2
- Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2
- implications of phosphorylation in p53 regulation
- Data suggest a model in which p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene to activate transcription. In addition, this study defines a novel mechanism utilized by the p53 tumor suppressor to regulate gene expression.
- MDM2 has been characterized as a protein that binds to and facilitates degradation of the tumor suppressor p53. Splice variants of MDM2 transcripts have been identified in both tumors and normal tissues.
- Hypophosphorylation of Mdm2 augments p53 stability. The degree of conservation in the central acidic domain of mouse and human Mdm2 proteins is high.
- The candidate tumor suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2.
- MAPK as an upstream regulator of mdm2 expression
- MDM2 is not required for p53 proteasomal degradation regulated by NADPH quinone oxidoreductase 1
- p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1.
- Results describe the thermodynamic and kinetic-binding parameters for the interaction between MDM2 and p53 proteins.
- MDM2 ubiquitination is enhanced by MDMX
- Mdm2 is sumoylated during nuclear translocation by RanBP2 and then further sumoylated once in the nucleus by PIASxbeta and PIAS1
- Overexpression of mdm2 was seen predominantly in blastoid mantle cell leukemia, seemed unrelated to gain of chromosome 12, did not reflect a high proliferative rate, but might indicate an alternative mechanism of inactivating p53.
- acetylation of p53 inhibited by its ubiquination
- MDM2 can promote p53 deacetylation by recruiting a complex containing HDAC1. Wild-type HDAC1 and MDM2 deacetylate p53 synergistically.
- The combined expression of adenovirus E1A, Ha-RasV12, and MDM2 is sufficient to convert a normal human cell into a cancer cell.
- Ubiquitination and degradation of p53 are largely controlled by Mdm2, an oncogenic E3 ligase.
- role of p53 binding domain in p53 regulation
- Data provide evidence of a role for MDM2 and CDK4 in the pathogenesis of carcinosarcoma.
- in glioblastoma multiforme patients a complex relationship exists between the Mdm2 expression and age
- Mdm2-mediated p53 ubiquitination is suppressed by HIF-1 alpha, which blocks Mdm2-mediated nuclear export of p53
- La antigen dependent activation of mdm2 translation might represent an important molecular mechanism involved in BCR/ABL leukemogenesis
- These data strongly suggest that Mdm2 functions as the ubiquitin ligase toward hNumb and that it induces its degradation in intact cells.
- Overexpression of the Mdm2 gene product may be important in the pathogenesis of penile verrucous carcinoma since Mdm2 is a negative regulator of p53
- It appears, that MDM2 overexpression, which may be p53-dependent, or also p53-independent plays an important role in leukemogenesis and/or disease progression.
- two upstream open reading frames of oncogene mdm2 may play a fundamental role in regulating expression of the mdm2 gene
- p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells.
- ubiquitination of MDM2 is cell cycle-regulated and MDM2 may play a role in cell cycle progression
- Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. Mdm2 serves as a ligase in ubiquitination of the IGF-1R and thereby causes its degradation by the proteasome system.
- MDM2 promotes ubiquitination and degradation of MDMX
- MDM2 regulates hdmx protein stability
- Ligase dead mutants of Mdm2 did not act in a dominant negative manner to reactivate p53 and they are not oncogenes in human mammary epithelial cells.
- MDM2 is regulated and degraded by GCL-1
- colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation.
- MDM2 has a role in DNA damage-induced MDMX degradation
- study of MDM2 protein binding to the N-terminal domain of p53
- HdmX is actively involved in the degradation of both p53 and Hdm2.
- Results imply that the current paradigm for understanding Mdm2 action during oncogenesis is incomplete, and its splice variants contribute to human cancer.
- PTEN inhibits MDM2 and protects p53 through both p13k/Akt-dependent and -independent pathways in ALL.
- The expression and structure of HDM2 in HL cell lines was studied. Several different spliced hdm2 transcripts (mdm-sv) including five new variants lacking a functional p53 binding site were characterized.
- Mdm2 is a regulator of cell growth and death [review]
- interaction with nucleic acids interferes with both Hdm2/Hdm2 complex formation and auto-ubiquitination of Hdm2 in vitro; although binding of Hdm2 to p53 is not inhibited by nucleic acids, Hdm2-mediated ubiquitination of p53 is significantly decreased.
- MDM-2 overexpression can block UV-induced cell cycle arrest and apoptosis by inhibiting P53 transcriptional activity
- L11 functions as a negative regulator of HDM2 and there might exist in vivo an L11-HDM2-p53 pathway for monitoring ribosomal integrity
- MDM2 amplification in soft tissue sarcoma patients was associated with a prognosis better than that of patients without the amplification. of the tumors with an MDM2 amplification, 40% also experienced loss of heterozygosity at 12q14-15.
- MDM2 directly inhibits p21waf1/cip1 function by reducing p21waf1/cip1 stability in a ubiquitin-independent fashion
- results show that low levels of Mdm2 activity induce monoubiquitination and nuclear export of p53, whereas high levels promote p53's polyubiquitination and nuclear degradation
- overexpression is related to the tumorigenesis and/or tumour progression of salivary gland neoplasms
- MDM2 acts as a transcriptional factor to modulate expressions of other genes involved in cell cycle regulation and transformation and was hypothesized that MDM2 directly affected NF-kappaB expression and function in a P53-independent manner.
- Upregulation of p14ARF paralleled with MDM2 inhibition contributes to p53 accumulation in the nucleus in radiation-treated breast cancer cells.
- MDM2 may regulate p53, depending on its levels in the cell.
- Data report the effects of peptide binding on the N-terminal p53-binding domain of human MDM2.
- No correlation between p53 accumulation and survival in bilharziasis associated bladder squamous cell carcinoma.
- MDM2 functions as a negative regulator of p21, an effect independent of both p53 and ubiquitination
- MDM2 regulates the stability of PCAF by ubiquitinating and degrading this protein
- results identify an interferon-responsive protein kinase family as a novel modifier of two components of the p53 pathway, MDM2 and p21(WAF1)
- acetyltransferases may modulate cellular p53 activity not only by modifying p53, but also by inactivating Mdm2
- Results show that growth factor stimulation, overexpression of Akt/PKB, or loss of PTEN resulted in enhanced expression of both HIF-1alpha and HDM2.
- CDK4, MDM2, SAS and GLI genes are amplified in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma
- Data reveal that controlled MDM2 degradation is an important new step in p53 regulation.
- potential of p53-C277Y to up-regulate MDM2 expression was similar to wild-type p53
- Mdm2 in female patients is an independent prognostic factor, associated with shorter survival in brain glioma.
- the MDM2-L5-L11-L23 complex functions to inhibit MDM2-mediated p53 ubiquitination and thus activates p53
- These results reveal that ribosomal protein L23 is another regulator of the p53-MDM2 feedback regulation involved in cell growth.
- Data show that, when overexpressed, ribosomal protein L23 inhibits HDM2-induced p53 polyubiquitination and degradation and causes a p53-dependent cell cycle arrest.
- MDM2 gene spans approximately 33 kb and is divided into 12 exons.
- Ras appears to attenuate p53 in SW480 cells by two independent regulatory mechanisms, the one leading to increased Mdm2-dependent p53 degradation and the other leading to a decrease in p53 transcription.
- Review of MDM2 which inhibits p53 degradation in head and neck cancers
- Epstein barr virus can indirectly enhance mdm2 gene expression in tumor cells that express this gene.
- the central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth
- MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form.
- identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro
- The RING domain of MDM2 mediates histone ubiquitylation and transcriptional repression.
- role of Cul4A in the MDM2-mediated proteolysis of p53
- A single nucleotide polymorphism is found in the MDM2 promoter and is shown to increase the affinity of the transcriptional activator Sp1, resulting in higher levels of MDM2 RNA and protein and the subsequent attenuation of the p53 pathway.
- Data suggest that MTBP differentially regulates the activity of MDM2 towards two of its most critical targets (itself and p53) and in doing so significantly contributes to MDM2-dependent p53 homeostasis in unstressed cells.
- finding that MYCN directly modulates baseline MDM2 levels suggests a mechanism contributing to the pathogenesis of neuroblastoma and other MYC-driven malignancies through inhibition of MYC-stimulated apoptosis.
- Mouse cells deficient for MK2 show reduced Mdm2 phosphorylation and elevated levels of p53 protein.
- Alternative MDM2 splicing is highly associated with lung cancer.
- Mdm2 activity could activate p53 tumor suppression REVIEW
- MDM2 has oncogenic transformational activities independent of p53--REVIEW
- MDM2 splice variant expression has been associated with advanced neoplastic disease--REVIEW
- MDM2 oncogene is overexpressed in more than forty different types of malignancies--REVIEW
- Regulation of the nuclear export of hdm2 mRNA provides a mechanism whereby mitogen-stimulated cells avoid p53-dependent cell cycle arrest or apoptosis by maintaining the dynamic equilibrium of the Hdm2-p53 feedback loop
- p73, through HDM2, can oppose p53 tumor suppressor function and possibly contribute to tumorigenesis
- Nbs1 is a novel p53-independent Mdm2 binding protein and links Mdm2 to the Mre11-Nbs1-Rad50-regulated DNA repair response
- The abundant expression of double-minute protein 2 (MDM2) in rheumatoid arthritis may be a contributing factor to the hypoapoptotic phenotype of lining tissue through its capacity to downregulate p53 levels and effects.
- MDM2 may have implications for glioma cell death susceptibility
- Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53.
- sites important for Hdm2-mediated ubiquitination of Hdmx after double-strand break induction
- alpains participate in the down-regulation of Mdm2 in the epidermis very rapidly after UV irradiation.
- p53, Bax, Bcl-2 and Mdm2 mRNA expression levels correlate with the malignant transformation of the uterine cervix
- protection of p53 from MDM2 by PTEN and the damage-induced activation of PTEN by phosphorylated p53 leads to the formation of an apoptotic amplification cycle in which p53 and PTEN coordinately increase cellular apoptosis
- HDM2 negatively affects the Chk2-mediated phosphorylation of p53.
- expression of p53, MDM2, and p21Waf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis
- MdmX can affect post-translational modification and stability of Mdm2 and p53 activity through interaction with ARF
- beta-arrestin has a role in ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase
- TP53 mutation has only a limited role in the transformation of lymphoma to diffuse large B-cell lymphoma, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent.
- overproduction of Mdm2, resulting from a naturally occurring SNP, inhibits chromatin-bound p53 from activating the transcription of its target genes.
- Results suggest that impaired deubiquitination of Hdmx/Hdm2 by HAUSP contributes to the DNA damage-induced degradation of Hdmx and transient instability of Hdm2.
- besides tumor protein p53 alterations, MDM2 gene deregulation seems to be an important event in hepatocarcinogenesis
- analysis of the more open conformation of the binding cleft of MDM2N (non-liganded)
- Data show that expression of the ErbB-4 ICD fragment leads to its constitutive association with and tyrosine phosphorylation of Mdm2.
- deletion of Mdm4 enhances the ability of Mdm2 to promote cell growth and tumor formation, indicating that Mdm4 has antioncogenic properties when Mdm2 is overexpressed
- GSK3-dependent phosphorylation of Mdm2 regulates p53 abundance
- ATM directly activates p53 while activating a safe-lock mechanism to inactivate the negative regulators of p53, Mdm2, and Mdmx [review]
- ARF may regulate p53 acetylation and stability in part by inhibiting tripartite motif-containing 28-MDM2 binding
- the p14ARF-p53-MDM2 pathway has a role in development of oral squamous cell carcinoma
- 2 promoter polymorphisms of MDM2 and evaluated their associations with risk of lung cancer
- p53-mdm2 binding is subtler than previously thought and involves global contacts such as multiple "non-contiguous" minimally structured motifs instead of being localized to one small helix mini-domain in p53 TAD
- The E3 ligase activity of MDM2 is redirected to MDMX after DNA damage and contributes to p53 activation.
- T309G polymorphism for MDM2 significantly decreases the age of onset for ALL in the pediatric population, particularly within Caucasian and black pediatric communities
- MDM2 stabilizes E2F1 protein through the E2F1 ubiquitination pathway.
- Studies reported the discovery of a third promoter (designated P3) in intron 3 of MDM2 gene, which contains a TATA-box element and p53-DNA-binding sequences.
- the p53 and MDM2 promoter polymorphisms do not appear to play a role on age of colorectal cancer onset in Lynch syndrome
- HIPK2 contributes to drug-induced modulation of MDM2 activity at transcriptional (through p53Ser46 phosphorylation) and posttranscriptional (through p53-independent subcellular re-localization and proteasomal degradation) levels.
- the p53-HDM2 interaction can be inhibited by a newly isolated hexylitaconic acid from the marine-derived fungus, Arthrinium
- Studies of MDM2 in more than 2000 breast carcinomas show that MDM2 is an independent negative prognostic marker.
- Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer.
- The MDM2 promotes Rb degradation in a proteasome-dependent and ubiquitin-independent manner.
- These findings suggest that overexpression of Mdm2 can perturb a RB pathway regardless of the p53 gene status, promoting carcinogenesis.
- MDM2 has critical roles in the regulation of p21 and E2F1 expression, stability and function [review]
- identification of a second binding site helps stabilize the interaction between HDM2 and p53 during p53 degradation
- MDM2 -309 allele and genotype frequencies did not differ between cases and controls, and ORs for breast cancer were close to the null in African-Americans and Whites.
- MDM2 antagonists alone or in combination with chemotherapeutic drugs may offer a new treatment option for B-CLL.
- N-terminal domain of USP7 binds two closely spaced 4-residue sites in both p53 and MDM2, falling between p53 residues 359-367 and MDM2 residues 147-159.
- Our data indicate that MDM2-SNP309 is a modifier of the age at colorectal cancer onset for patients whose tumors have a wild-type p53 gene.
- IFIX alpha1 isoform functions as a tumor suppressor by repressing HDM2 function
- Results indicate that the MDM2 G/G genotype of SNP309 is associated with lung cancer risk with an odds ratio of 1.62 (95% CI: 1.06-2.50).
- MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53
- analysis of the role of p53 substrate conformation in controlling MDM2-dependent ubiquitination of p53 and identification of a link between substrate misfolding and susceptibility to ubiquitination
- p90Rsk-mediated modulation of Hdm2 nuclear is linked to cytoplasmic shuttling with the diminished ability of p53 to regulate cell cycle checkpoints that ultimately leads to transformation
- HDM2 can selectively down-regulate the transcription function of p53 without either degrading p53 or affecting the interaction of p53 with target promoters
- Jab1 is required to remove post-translationally modified p53 in coordination with mdm2
- Data show that nuclear accumulations of p53 and Mdm2 are accompanied by reductions in c-Abl and p300 in zinc-depleted human hepatoblastoma cells.
- study showed that MDM2 amplification and overexpression might be an early event in the growth of human gliomas
- interaction of free arrestins with JNK3 and Mdm2 and their ability to regulate subcellular localization of these proteins may play an important role in the survival of photoreceptors and other neurons
- Review. An alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta via Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63.
- levels are reduced by nucleolin
- L11, unlike L5 and L23, differentially regulates the levels of ubiquitinated p53 and MDM2 and inhibits the turnover and activity of MDM2 through a post-ubiquitination mechanism
- Collectively, our results suggest that a loss of the cisplatin sensitivity is at least in part due to a lack of cisplatin-induced p53 phosphorylation, and p73 might cooperate with MDM2 to be involved in this process.
- Among homozygous carriers of the common MDM2 SNP309 allele, a mutant p53 status (risk ratio of death = 2.33, 95% CI = 1.08 to 5.03)and aberrant p53 protein expression(RR = 2.61, 95% CI = 1.22 to 5.57)in breast tumors were associated with poor survival.
- Data suggest that the G-allele of SNP309 accelerates colorectal tumour formation only in women.
- MDM2-single nucleotide polymerase 309 favours tumour selection of non-dominant negative P53 mutations in colorectal cancer, which also show an earlier age of tumour onset.
- PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells.
- Although the interaction between the N-termini of mdm2 and p53 blocks the transactivation activity of p53, the interaction between the central domain of mdm2 and the core domain of p53 is critical for the ubiquitination and degradation of p53.
- p53 binding to the central domain of Mdm2 is regulated by phosphorylation
- MDM2 is therefore considered one of the mineralocorticoid-responsive genes that regulates cell proliferation of vascular smooth muscle cell (VSMCs) induced by MR-mediated aldosterone stimulation.
- These results suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development.
- Gene amplifications are important prognostic markers for soft tissue sarcomas.
- Hdmx is an important determinant of the outcome of P53 activation
- The MDM2 promoter SNP309 is associated with the presence of hepatocellular carcinoma in Japanese patients with chronic hepatitis C.
- Study evaluated Pirh2, MDM2, p53 and p21 expression after DNA damage using cancer cell lines containing wildtype, mutant and null p53 and found that unlike MDM2, Pirh2 expression was not affected by the presence of wildtype p53 in the cancer cells.
- Results report the solution structure of the C2H2C4 RING domain of Hdm2(429-491), which reveals a symmetrical dimer with a unique cross-brace zinc-binding scheme.
- A novel role for MDM2 in regulating cell adhesions by a mechanism that involves degrading and down-regulating the expression of E-cadherin via an endosome pathway.
- The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder
- TP53 germline mutation carriers with SNP309 G allele have earlier onset of tumours; higher prevalence of MDM2 SNP309 homozygous carriers in TP53-negative group suggests allele contributes to cancer susceptibility in Li-Fraumeni syndrome & related familie
- insulin-like growth factor-1 alters Mdm2-mediated GRK2 degradation, leading to enhanced GRK2 stability and increased kinase levels
- When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased
- Stress-induced HDM2(ALT1) regulates HDM2 at two levels, RNA and protein, further modulating the p53-HDM2 interaction or interactions of HDM2 with other cell cycle regulatory proteins.
- Alternate forms of MDM2 are detected after UV irradiation. Alternate forms of MDM2 place selective pressure on the cells to acquire additional alterations in the p53 pathway.
- the reduction of KAP1 levels promotes p53-dependent p21 induction and inhibits cell proliferation in actinomycin D-treated cells.
- analysis of mechanism of formation of the principal MDM2 isoforms, differential effects of p53 on the production of these isoforms, and differential abilities of human MDM2 isoforms as regulators of the MDM2/TSG101 and p53/MDM2 feedback control loops
- MDM2 single nucleotide polymorphism accelerates familial breast carcinogenesis independently of estrogen signaling
- MDM2 T309G polymorphism is associated with bladder cancer
- Results indicate the G allele of MDM2 SNP309 might have a protective effect on disease development in HNPCC patients and that age of diagnosis of CRC is not associated with MDM2 SNP309 or TP53 R72P either as single SNPs or combined.
- Cancer-associated missense mutations targeting MDM2's central zinc finger disrupt the interaction of MDM2 with L5 and L11.
- AURKA and MDM2 were identified as interesting novel amplified genes in juvenile angiofibromas
- p53 mediates the suppression of TR3 on MDM2 at both transcriptional and post-transcriptional level and suggest TR3 as a potential target to develop new anticancer agents that restrict MDM2-induced tumor progression.
- functions of the extreme C-terminus of MDM2 can be provided by MDMX
- Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity
- p53 and Ki-67 were expressed with increasing frequency, and bcl-2, p21, and mdm-2 with decreasing frequency in thyroid carcinoma progression. p27 and cyclin D1 were expressed in <15% of cases, with a trend toward decreasing expression.
- p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory loop, but also profoundly impact on the transcriptome through various CBP/p300 and P/CAF interacting proteins.
- Mdm2 and TAFII250 associate in cultured cells; the acidic domain of MDM2 is required for TAFII250-stimulated ubiquitylation and degradation of p53.
- 5-FU treatment triggers a ribosomal stress response so that ribosomal proteins L5, L11, and L23 are released from ribosome to activate p53 by ablating the MDM2-p53 feedback circuit
- Both kinetics and free energy landscape analyses indicate that bound MDM2 unfolds in the order of p53 unbinding, tertiary unfolding, and finally secondary structure unfolding.
- S7 binds to MDM2, in vitro and in vivo, and the interaction between MDM2 and S7 leads to modulation of MDM2-p53 binding by forming a ternary complex among MDM2, p53 and S7.
- Review discusses the important regulatory roles of MDMX during the p53 response to ribosomal stress.
- BOX-V motif of p53 has evolved the capacity to bind to enzymes that mediate either p53 phosphorylation or ubiquitination
- These findings establish HIPK2 as an MDM2 target and support a model in which, upon nonsevere DNA damage, p53 represses its own phosphorylation at Ser46 due to HIPK2 degradation.
- Nutlin efficiently stabilized p53 and induced downstream p53 dependent transcription and apoptosis in liposarcoma cells with amplified MDM2 in vitro
- Arrestins recruit ERK1/2 and the E3 ubiquitin ligase Mdm2 to microtubulesin cells, similar to the arrestin-dependent mobilization of these proteins to the receptor.
- analysis of haplotype structure and selection of the MDM2 oncogene in humans
- results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest
- Our analysis reveals interactions of HDM2 with the ribosomal translation elongation factor EF1alpha, 40S ribosomal protein S20, tubulins, glyceraldehyde 3-phosphate dehydrogenase, and a proteolysis-inducing factor dermicidin.
- The -309 SNP in MDM2 is associated with increased MDM2 transcription but there are inconclusive results with respect to breast cancer risk
- Colocalization and interaction of MDM2-A and MDM2-B with full-length MDM2 in the nucleus have important physiologic consequences, for example, deregulation of p53 activity.
- CARF may exert a vital control on p53-HDM2-p21(WAF1) pathway that is central to the cell cycle control, senescence, and DNA damage response of human cells
- Che-1 as a new Pin1 and HDM2 target and confirm its important role in the cellular response to DNA damage.
- findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of nasopharyngeal carcinoma in Chinese population
- MDM2 overexpression is associated with copy number gains of the MDM2 locus in single tumors, but not with the recently reported MDM2 promoter SNP309.
- Both ionizing radiation and daunorubicin treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3.
- ubiquitination-mediated repression of p53 by Mdm2 acts at least, in part, through inhibiting the sequence-specific DNA binding activity
- Nutlin-3 could protect both endogenous and exogenous p53 from MDM2-mediated inactivation
- a trimeric protein complex containing p53, Mdm2 and HAUSP can exist in vivo, despite mutually exclusive binding, with Mdm2 serving as a binding mediator for p53 and HAUSP
- in this study population, SNP309 affected MDM2 protein level, but had no significant involvement in glioma tumorigenesis
- immunoreactivity of p53, MDM2, WAF1, and BCL-2 were measured in soft tissue sarcomas cases consisting of 54 low-grade, 40 intermediate-grade, and 58 high-grade sarcomas
- findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse overall survival among early-stage non-small-cell lung cancer patients, particularly those with squamous cell histology
- SNP309 of HDM2 is a frequent event in bladder cancer, related to earlier onset of superficial disease and TP53 mutation status
- nutlin-3A stabilized p53 by preventing MDM2-mediated p53 degradation in and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL)
- Results suggest that the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC.
- MDM2 SNP309 is not associated with glioblastoma risk, and is not a prognostic factor.
- LMP1 of Human herpesvirus 4 augments MDM2 protein expression in a dose-dependent level and leads to a drastic accumulation of ubiquitinated MDM2 species. This effect is associated with the stability of MDM2 modulated by LMP1.
- Nutlin-3 abrogates both pre-osteoclastic proliferation and differentiation through a p53-dependent pathway
- the MDM2 and MDMX complex has a role in abundance and activity of p53
- analysis of the p53-Mdm2 feedback loop using protein lysate microarrays
- In lung cancer patients, p53 accumulation could be due to a decrease in full-length MDM2 isoform together with an increase of the 57-kDa MDM2 isoform that was unable to stimulate p53 degradation.
- Rhabdomyosarcoma cells overexpressing MDM2 abrogated ceramide-mediated p21(Cip1/Waf1) induction, G(2) arrest and the late ensuing apoptosis.
- Single nucleotide polymorphisms are an independent adverse prognostic factor for survival in renal cell carcinoma.
- P53 Arg72Pro and MDM2 T309G polymorphisms contribute to the risk of developing stomach cancer.
- damage-activated switch in Hdm2 ubiquitin ligase preference from P53 to itself and Hdmx is central to P53 activation
- overexpression of Mdm2 caused by overexpression of SUMO-1 may be involved in tumor aggressiveness even in patients with early stage oral squamous cell carcinoma
- MDM2 overexpression is not related to decreased survival length in women operated on for advanced-stage EC.
- Arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin 'frozen' in the basal state.
- The up-regulation of PTEN inhibited Akt and MDM2, which enhanced the level of p53, thereby inducing G(2)/M arrest and apoptosis.
- the WNV capsid (WNVCp) is capable of binding to and sequestering HDM2 into the nucleolus.
- HCMV uses a shift from p53 to HDM2 ubiquitination and destabilization to obtain protracted high levels of p53, while promoting cell cycle traverse
- Deficiencies in the function of core DNA replication machinery (e.g., transgenic Mdm2) that are compatible with development and survival nonetheless result in a chronic phenotype leading to stem cell deficiency in multiple tissues and cancer.
- The results indicate protective associations of p53 Arg72Pro heterozygous variant with postmenopausal and MDM-2 SNP309G along with p53 Arg72Pro heterozygous variant with premenopausal breast cancer risk.
- Activation of AKT, possibly through the PI3K-AKT pathway, is an important component of ASCC tumorigenesis that contributes to MDM2 and TP53 accumulation in the nucleus.
- SNP309 of MDM2 alone has little or no effect on the risk of common cancers, but it might modify the time of tumor onset and prognosis
- The apoptosis of DNA-damage-induced p53 is reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism
- ATP binding function of MDM2 can mediate its chaperone function toward the p53 tumor suppressor
- CSN5 is a pivotal regulator for both p53 and MDM2
- In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone.
- this large collaborative study did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer
- This is an overview/review of the p53-proto-oncogene protein MDM2 module and its associated pathways from a systems biology perspective. In normal cells, MDM2 negatively regulates the activity of p53.
- Wip1 acts as a gatekeeper in the Mdm2-p53 regulatory loop by stabilizing Mdm2 and promoting Mdm2-mediated proteolysis of p53.
- Expression of MDM2 in rhabdomyosarcoma cells transcriptionally repressed p65RelA and suppressed NFkappaB activity, resulting in a reduced growth rate and enhanced apoptosis.
- MDM2 levels were significantly lower in temporal lobe epilepsy patient brains
- a strong gene-smoking interaction was observed between the MDM2 SNP309 and nonsmall cell lung cancer risk
- Mutation of the IP6-binding sites impair oligomerization, reduce interaction with Mdm2, and inhibit p53-dependent antiproliferative effects of beta-arr2
- SNP309 MDM2 may not be a risk factor for cervical cancer.
- MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.
- Report mdm2 expression in abberant crypt foci and colorectal neoplasms.
- MDM2 SNP309 serves as a low-penetrance susceptibility tumor marker
- These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases.
- Mdm2 is a sensitive biomarker for certain types of genotoxicity.
- A novel role for the HDM2 oncoprotein in the regulation of angiogenic factors in renal cell carcinoma.
- High p53 expression level with low MDM2 and p14 ARF levels may be the characteristic features of low differentiated endometrial carcinoma.
- There is a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS-ERK and MDM2.
- MDM2 was amplified and overexpressed in well-differentiated and dedifferentiated liposarcomas
- Data report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b).
- These results indicate that in thyroid cancer cells, TAp73alpha is able to increase p53 protein level and function by interfering with Mdm2-mediated p53 degradation.
- SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2.
- Endogenous Mdm2 does not regulate its own stability by self-ubiquitination.
- MDM2 SNP309, alone or in combination with TP53 R72P, was not associated with oligodendroglial tumors.
- Study found that Tip60 is capable of selectively inhibiting the Mdm2-mediated conjugation of Nedd8 to p53, whereas it did not affect p53 ubiquitination; hence, the two different E3 ligase activities of Mdm2 can be regulated individually.
- High-level amplification of MDM2 at 12q13-15 was observed in 4/7 cases of liposarcoma.
- Although the MDM2 SNP309 G allele is a risk factor for breast cancer, it does not accelerate, but delays the onset of the sporadic disease in Chinese women.
- CARF exerts a vital control on the p53-HDM2-p21WAF1 pathway that is frequently altered in cancer cells.
- the MDM2 SNP309G allele was associated with reduced risk of leukaemia. No other association was found between SNP309 and other parameters in both males and females. Thus, the data highlights ethnic differences in the effects of this SNP on cancer risk.
- The prevalence of MDM2 gene amplifications and single nucleotide polymorphism 309 in 284 colorectal tumors in relation to TP53 mutational status and genomic instability, is analyzed.
- PKC epsilon mediates TRAIL resistance by Akt-mediated phosphorylation of Hdm2 resulting in suppression of p53 expression and downregulation of Bid in breast cancer cells
- isosilybin B treatment enhances the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation-dependent AR ubiquitination and its degradation by proteasome
- Rb antagonizes gankyrin to inhibit MDM2-mediate p53 ubiquitination in cancer cells and suggest that the status of both p53 and Rb is important for efficacy of cancer chemotherapy.
- Our findings suggested that the T309G polymorphism of Mdm2 was not associated with an increased risk for gastric cancer in Korean population.
- In stage III non-small cell lung cancer, there was a significant association between TTF-1 and Mdm2
- stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells
- Smo mutants augment p53 binding to the E3 ubiquitin-protein ligase Mdm2 and promote p53 ubiquitination.
- Neither germline variants in p53 nor MDM2 SNP309 play an underlying role in the development of very early onset CRC
- CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death.
- MDM2 single-nucleotide polymorphism is associated with the early development of hepatocellular carcinoma in Korean patients with chronic HBV infection.
- MDM2 SNP309 was not associated with susceptibility to or age of onset of OSCC or OSF. The MDM2 SNP G/G polymorphism was associated with poor OS in advanced OSCC, and the OS and DSF of irradiated patients.
- These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function.
- an interactive effect was detected such that MDM2 TT TP53 Arg/Arg double homozygotes, and individuals carrying both a MDM2 G allele and a TP53 Pro allele, were at increased risk of t-AML
- Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences.
- DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of diffuse large B-cell non-Hodgin lymphoma patients.
- MDM2 regulates dihydrofolate reductase activity through monoubiquitination.
- Pim-1 induces the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma
- The MDM2 SNP309 genotype influencing MDM2 expression levels was identified as an additional independent risk factor in B-CLL.
- NFBD1 directly interacts with MDM2 and increases its stability.
- bronchial squamous cell carcinoma showed increased MDM2 (Murine double minute clone 2) staining at mild dysplasia.
- TIP60 and p73beta through MDM2 in the transcriptional regulation of cellular apoptosis
- MDM2 amplification was observed in a small portion of pleomorphic sarcomas and high-grade sarcomas other than dedifferentiated liposarcomas.
- Modulation of HDM2 expression could play an important role in tumor angiogenesis and the metastatic process via transcriptional regulation of VEGF.
- the MDM2 -309 T/G promoter single nucleotide polymorphism has no influence on disease characteristics in chronic lymphocytic leukemia
- the MDM2 G/G and T/G-SNP309 alleles are markers of increased predisposition to tumor development and disease aggressiveness in neuroblastoma
- the novel MDM2 promoter C1797G polymorphism may be a marker for genetic susceptibility to bladder cancer in Chinese populations
- Elevated MDM2 boosts the apoptotic activity of p53-MDM2 binding inhibitors by facilitating MDMX degradation.
- data clearly show neither association between SNP309 and cancer risk, nor the responsibility of G allele for increased MDM2 or decreased of p53 protein levels in human primary breast tumors.
- interaction of PI3K/Akt/mTOR and p53 pathways after their simultaneous blockade using the dual PI3K/mTOR inhibitor PI-103 and the Mdm2 inhibitor Nutlin-3.
- CK2 is tightly associated with TAFII250 and is the principal activity responsible for TAFII250-mediated phosphorylation of Mdm2.
- The Mdm2 allele may be associated with longer length of stay. However, it does not appear to influence any other clinical characteristics, nor can it be used to predict clinical outcome in sepsis
- The G allele of the MDM2 -309T/G polymorphism is associated with 2- to 3-fold increase risk and progression of pancreatic adenocarcinoma and a corresponding decrease in survival.
- RASSF1A associates with MDM2 and death-domain-associated protein (DAXX) in the nucleus, thereby disrupting the interactions between MDM2, DAXX, and the deubiquitinase, HAUSP, and enhancing the self-ubiquitin ligase activity of MDM2.
- An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway.
- Report relationship of Ki67, TP53, MDM-2 and BCL-2 expressions with WHO 1973 and WHO/ISUP grades, tumor category and overall patient survival in urothelial tumors of the bladder.
- MDM2 SNP309 and p53 Arg72Pro polymorphisms might influence the clinical outcome of transitional cell carcinoma of the bladder (TCCB) in a distinctive way between superficial TCCB and invasive TCCB.
- This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk.
- NIAM is a nuclear interactor of ARF and Mdm2
- data are consistent with a model in which Hdmx attenuates p53-dependent activation of the intrinsic apoptotic pathway, and that this occurs upstream of Bax activation
- We observed a significant inverse association between MDM2 expression and tumor invasion.Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression.
- Ubiquitin over-expression promotes the destabilization of the ubiquitin protein ligase E6AP, by a mechanism involving self-ubiquitination, and the stabilization of p53.
- c-Cbl is a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis
- These results indicate that acidic domain of MDM2 provides essential information for acetyltransferase p300 and deacetylase HDAC1 and is indispensable for MDM2 to negatively regulate the acetylation of p53.
- Overexpression of MDM2 and MDM4 is not a necessary step in retinoblastoma development.
- Mdm2 induces mono-ubiquitination of FOXO4
- hdmX mRNA levels are kept low following genotoxic stress
- Accelerated DNA repair required both the NBS1 protein and Hdm2, accompanied by phosphorylation of Hdm2, dissociation of NBS-1 and Hdm2, inhibition of NBS-1 degradation, and accelerated phosphorylation of ATM.
- MDM2 snp309 as predictor for sensitivity of B-CLL cells to the MDM2 inhibitor nutlin-3a.
- inhibition of E2F1 by MDM2 was stimulated by ATP & mutation of the ATP-binding domain of MDM2 (K454A) prevented ATP-stimulated inhibition of E2F1; data support a role for the ATP-binding domain in altering the protein-protein interaction function of MDM2
- STX6 can be induced by DNA damage and Mdm2 inhibitor Nutlin-3 in a p53-dependent manner.
- findings indicate that elevated MDM2 mRNA levels in tumours with MDM2 amplification are preferentially driven by the P1 promoter and that the P2 promoter is not only regulated by p53 but also by other transcription factor(s)
- there was no association between the MDM2 (Mdm2 p53 binding protein homolog)T309G polymorphism and susceptibility or course of disease in patients with Wegeners granulomatosis
- These studies provide the first insights into the molecular basis through which Arf nullifies the p53-inhibiting activity of Hdm2, indirectly activating the tumor-suppressor function of p53 in mammalian cells.
- These results provide evidence for the potential involvement of MDM2 SNP309 in pigmentary traits.
- the presence of conserved and non-conserved interactions along the conformational transition pathway that may be exploited in the design of selective and dual modulators of MDM2 activity
- SNP309G/G is associated with poor prognostic breast cancer features in the Scottish population; a novel SNP, SNP285, that is in linkage disequilibrium with SNP309, may also have a role in breast tumorigenesis
- No evident association between SNP309 and event free survival was found. The lack of association between SNP309 and MYCN status indicates that MDM2 SNP309 may be a new independent prognostic factor for stage 4 NB.
- Increased MDM2 expression and/or MDM2 amplification can be employed to aid discrimination of inflammatory well-differentiated liposarcoma from fibroinflammatory mimics
- The levels of HDM2 transcripts originating from the constitutive P1 and p53-sensitive P2 promoter in 133 soft tissue sarcomas was correlated the results with the age of diagnosis and the patients' outcome.
- Mdm2 regulates p53 levels also by targeting ribosomal protein L26 for polyubiquitylation and proteasomal degradation.
- Although the MDM2 SNP309 does not portend decreased survival, the increased incidence of the mutant G allele in patients with glioblastoma multiforme (GBM) suggests a potential role in the molecular pathogenesis of GBM.
- demonstrated no evidence for association of MDM2 SNP 309 or TP53 Arg72Pro allelic variants alone, or in combination, with overall survival (Figure 1A), progression free survival, relapse free survival or time to transformation
- Hdm2 is expressed in pancreatic cancer cells as a result of activated Ras signaling, and regulates cellular proliferation and the expression of target genes by p53-independent mechanisms.
- nucleoplasmic relocation of nucleostemin during nucleolar disassembly safeguards the G2-M transit and survival of continuously dividing cells by MDM2 stabilization and p53 inhibition.
- neither the TP53 Arg72Pro polymorphism nor the MDM2 SNP309 contributes significantly to either susceptibility or disease severity in systemic lupus erythematosus
- results support the hypothesis that p53 function is suppressed by aberrant HDM2 activity and suggest the possibility of targeting the p53-HDM2 regulatory axis as a therapeutic strategy in synovial sarcoma
- RYBP interacts with MDM2 & decreases MDM2-mediated p53 ubiquitination. The RYBP-binding domain of MDM2 was mapped to residues 180-298.
- p53-Mdm2 protein-protein and p53 mRNA-Mdm2 interactions affect Mdm2-mediated control of p53 expression using the Phe19Ala p53 mutant.
- The authors report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif.
- MDM2 SNP309 genotype is associated with the risk of breast cancer and an earlier age of onset in Taiwanese women.
- The authors found that liberation of p53 through chemical antagonism of one of its major ubiquitin ligases, MDM2, using the small-molecule Nutlin-3 led to apoptosis of established LCLs and suppressed EBV-mediated transformation of primary B cells.
- Mdm2-mediated control of p53 synthesis and degradation has evolved in the p53 mRNA sequence and its encoded amino acids.
- 14-3-3 proteins bind to Pim kinase-phosphorylated Ser166 and Ser186 on the human Mdm2, but not to protein kinase B/Akt-phosphorylated Ser166 and Ser186.
- The combination of the MDM2 SNP309 and the three TP53 polymorphisms appear to be related to a higher grade of endometrial cancer.
- MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription